This application creates a Specialized Program of Research Excellence (SPORE) in Breast Cancer at Harvard University and within the newly configured Dana-Farber/Harvard Cancer Center. The Dana- Farber/Harvard SPORE includes investigators from all Harvard-affiliated hospitals in Boston and from the Harvard Medical School and School of Public Health. Eight major projects are supported: Project 1 will translate findings from epidemiology into improved risk modes and begins a novel preventive clinical trial. Project 2 seeks new susceptibility genes, and will test their effects in at-risk and affected women. Project 3 applies discoveries about BRCA1 and BRCA2 to develop tractable functional assays. These investigations will be integrated by creation of the High Risk Patients and Families Core Resource, which includes all Harvard hospitals and clinics. Project 4 will seek and utilize genes discovered in early-stage breast cancer to predict progression and behavior. Project 5 will complement gene discovery by functional screens for gene effects in breast cancer progression in assays also applicable to screen small- molecule inhibitors. Project 6 creates animal models of the Tissue and Pathology ore services will integrate these studies. Project 7 addresses potentially inaccurate perceptions of women with newly diagnosed intraductal cancer, drawing on large populations and rapid case ascertainment. The Clinical Data and Data Management & the Biostatistics Cores Developing Projects and Resources, and to support the Career Development award to new translational scientists. Several strategies will provide a flexible and changing research agenda. A large number of events and activities will integrate and promote planning for the future.